The primary function of articular cartilage is to serve as a bearing material for diarthrodial joints. As part of our recent studies, we have demonstrated from theory and experiments that cartilage can provide efficient lubrication even under boundary friction, primarily because its interstitial water may pressurize considerably under loading. In this application, we propose to follow-up on these findings by addressing specific questions related to the functional effectiveness of the lubrication mechanism in diarthrodial joints: a) Since the friction coefficient is observed to increase over time to functionally detrimental values under laboratory testing conditions, what makes it stay sufficiently low under physiological loading conditions in situ? b) How effective are the boundary lubricants in synovial fluid, after accounting for the role of interstitial fluid load support? c) Is there a functionally significant mixed lubrication regime in the initial response to joint loading during which lubricant is temporarily trapped between articular surfaces, and if so, does the duration of this mixed regime depend on the type of lubricant? While it may be attractive from the clinical and commercial perspective to consider joint lubrication in terms of a phenomenon arising from synovial fluid and its constituents (e.g., intra-articular injection of hyaluronan and other "lubricants"), their relative contribution to the low frictional properties of articular cartilage are not well understood. With an original theoretical framework, validated using novel experimental techniques developed over the past two granting periods that clearly describe how articular cartilage is able to exhibit extremely low friction coefficients even in the absence of synovial fluid, we now propose studies to determine the contribution of boundary lubricants in synovial fluid to the functional effectiveness of the lubrication mechanism in diarthrodial joints. Our proposal is timely in light of the recent resurgence of interest in proteins in synovial fluid or in the superficial zone of articular cartilage that may assist in the tribological response. To investigate our hypotheses, the proposal incorporates some novel applications of Atomic Force Microscopy (AFM), Total Internal Reflectance Fluorescence (TIRF) microscopy, and Scanning Confocal Microscopy (SCM) techniques.